Circulating fibrocytes traffic to the lung in murine acute lung injury and predict outcomes in human acute respiratory distress syndrome: a pilot study.

BACKGROUND: Fibrosis is an integral component of the pathogenesis of acute lung injury and is associated with poor outcomes in patients with acute respiratory distress syndrome (ARDS). Fibrocytes are bone marrow-derived cells that traffic to injured tissues and contribute to fibrosis; hence their concentration in the peripheral blood has the potential to serve as a biomarker of lung fibrogenesis. We therefore sought to test the hypothesis that the concentration and phenotype of circulating fibrocytes in patients with ARDS predicts clinical outcomes. METHODS: For the animal studies, C57Bl/6 mice were infected with experimental Klebsiella pneumoniae in a model of acute lung injury; one-way ANOVA was used to compare multiple groups and two-way ANOVA was used to compare two groups over time. For the human study, 42 subjects with ARDS and 12 subjects with pneumonia (without ARDS) were compared to healthy controls. Chi-squared or Fisher's exact test were used to compare binary outcomes. Survival data was expressed using a Kaplan-Meier curve and compared by log-rank test. Univariable and multivariable logistic regression were used to predict death. RESULTS: In mice with acute lung injury caused by Klebsiella pneumonia, there was a time-dependent increase in lung soluble collagen that correlated with sequential expansion of fibrocytes in the bone marrow, blood, and then lung compartments. Correspondingly, when compared via cross-sectional analysis, the initial concentration of blood fibrocytes was elevated in human subjects with ARDS or pneumonia as compared to healthy controls. In addition, fibrocytes from subjects with ARDS displayed an activated phenotype and on serial measurements, exhibited intermittent episodes of markedly elevated concentration over a median of 1 week. A peak concentration of circulating fibrocytes above a threshold of > 4.8 × 106 cells/mL cells correlated with mortality that was independent of age, ratio of arterial oxygen concentration to the fraction of inspired oxygen, and vasopressor requirement. CONCLUSIONS: Circulating fibrocytes increase in a murine model of acute lung injury and elevation in the number of these cells above a certain threshold is correlated with mortality in human ARDS. Therefore, these cells may provide a useful and easily measured biomarker to predict outcomes in these patients.

Outcomes and Long-Term Survival of Adolescent and Young Adult Patients Admitted to the Intensive Care Unit Following Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Experience of 152 Patients.

BACKGROUND AND OBJECTIVES: Prognostic factors reliably predicting outcomes for critically ill adolescent and young adult (AYA) patients undergoing allogeneic hematopoietic cell transplantation (allo-HSCT) are lacking. We assessed transplant and intensive care unit (ICU)-related factors impacting patient outcomes. PATIENTS AND METHODS: AYA patients who underwent allo-HSCT and required ICU admission at a Tertiary care Centre, during the period of 2003-2013, were included in this retrospective review. This was a non-interventional study. Only outcomes after the first allo-HSCT and index ICU admissions were analyzed. Disease-, transplant-, and ICU-related variables were analyzed to identify risk factors predictive of survival. RESULTS: Overall, 152 patients were included (males, 60.5%); median age at transplantation was 24 years (interquartile range [IQR] 18-32.5); median age at admission to the ICU was 25.8 years (IQR 19-34). Eighty-four percent underwent transplantation for a hematological malignancy; 129 (85%) received myeloablative conditioning. Seventy-one percent of ICU admissions occurred within the first year after allo-HSCT. ICU admission was primarily due to respiratory failure (47.3%) and sepsis (43.4%). One hundred and three patients (68%) died within 28 days of ICU admission. The 1- and 5-year overall survival rates were 19% and 17%, respectively. Main causes for ICU-related death were refractory septic shock with multiorgan failure (n = 49, 32%) and acute respiratory distress syndrome (ARDS) (n = 39, 26%). Univariate analysis showed that ICU mortality was associated with an Acute Physiology and Chronic Health Evaluation (APACHE) II score >20, a sequential organ failure assessment (SOFA score) > 12, a high lactate level, anemia, thrombocytopenia, leukopenia, hyperbilirubinemia, a high international normalized ratio (INR) and acute graft-versus-host disease (GVHD). Multivariate analysis identified thrombocytopenia, high INR, and acute GVHD as independent predictors of mortality. CONCLUSIONS: In AYA allo-HSCT patients admitted to the ICU, mortality remains high. Higher SOFA and APACHE scores, the need for organ support, thrombocytopenia, coagulopathy, and acute GVHD predict poor outcomes.

Enhancing Expert Panel Discussions in Pediatric Palliative Care: Innovative Scenario Development and Summarization With ChatGPT-4.

This study presents a novel approach to enhance expert panel discussions in a medical conference through the use of ChatGPT-4 (Generative Pre-trained Transformer version 4), a recently launched powerful artificial intelligence (AI) language model. We report on ChatGPT-4's ability to optimize and summarize the medical conference panel recommendations of the first Pan-Arab Pediatric Palliative Critical Care Hybrid Conference, held in Riyadh, Saudi Arabia. ChatGPT-4 was incorporated into the discussions in two sequential phases: first, scenarios were optimized by the AI model to stimulate in-depth conversations; second, the model identified, summarized, and contrasted key themes from the panel and audience discussions. The results suggest that ChatGPT-4 effectively facilitated complex do-not-resuscitate (DNR) conflict resolution by summarizing key themes such as effective communication, collaboration, patient and family-centered care, trust, and ethical considerations. The inclusion of ChatGPT-4 in pediatric palliative care panel discussions demonstrated potential benefits for enhancing critical thinking among medical professionals. Further research is warranted to validate and broaden these insights across various settings and cultures.

The Saudi Critical Care Society practice guidelines on the management of COVID-19 in the ICU: Therapy section.

BACKGROUND: The rapid increase in coronavirus disease 2019 (COVID-19) cases during the subsequent waves in Saudi Arabia and other countries prompted the Saudi Critical Care Society (SCCS) to put together a panel of experts to issue evidence-based recommendations for the management of COVID-19 in the intensive care unit (ICU). METHODS: The SCCS COVID-19 panel included 51 experts with expertise in critical care, respirology, infectious disease, epidemiology, emergency medicine, clinical pharmacy, nursing, respiratory therapy, methodology, and health policy. All members completed an electronic conflict of interest disclosure form. The panel addressed 9 questions that are related to the therapy of COVID-19 in the ICU. We identified relevant systematic reviews and clinical trials, then used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach as well as the evidence-to-decision framework (EtD) to assess the quality of evidence and generate recommendations. RESULTS: The SCCS COVID-19 panel issued 12 recommendations on pharmacotherapeutic interventions (immunomodulators, antiviral agents, and anticoagulants) for severe and critical COVID-19, of which 3 were strong recommendations and 9 were weak recommendations. CONCLUSION: The SCCS COVID-19 panel used the GRADE approach to formulate recommendations on therapy for COVID-19 in the ICU. The EtD framework allows adaptation of these recommendations in different contexts. The SCCS guideline committee will update recommendations as new evidence becomes available.

Elevated alanine aminotransferase levels in HIV-infected persons without hepatitis B or C virus coinfection.

BACKGROUND: Mortality related to human immunodeficiency (HIV) has improved with the use of antiretroviral therapy; however, liver disease-related mortality remains a major concern for the HIV population. Elevation of alanine aminotransferase (ALT) has been noted in HIV-infected persons even without viral hepatitis infection. OBJECTIVE: The objective of this study was to determine the incidence and prevalence of chronic alanine ALT elevation among patients infected with HIV who are negative for hepatitis B or C infection. DESIGN: Retrospective chart review. SETTINGS: We reviewed the medical records of all patients infected with HIV who had been treated from November 2002 to December 2010. PATIENTS AND METHODS: Patients with an unknown or positive HBV or HCV infection status were excluded. We identified patient demographics, route of transmission, peak viral load, and nadir CD4 count. RESULTS: We followed 440 patients for up to 2265 person-years. A total of 123 patients developed chronically elevated ALT levels, with an incidence of 5.8 cases per 100 person-years. Chronically elevated ALT levels were associated with high HIV viral load, mean body mass index, and diabetes mellitus. We found exposure to lamivudine in 58% of the patients, efavirenz in 41%, and zidovudine in 38%. Abdominal ultrasounds revealed fatty liver in 20 of 39 (51%) of the patients. CONCLUSION: Among patients without viral hepatitis coinfection, the prevalence and incidence of chronic elevated ALT levels were high and accompanied by high HIV RNA levels and increased BMI. LIMITATIONS: The limitations of this report are its retrospective nature and lack of a control group.

Viral hepatitis B and C in HIV-infected patients in Saudi Arabia.

BACKGROUND AND OBJECTIVES: Hepatitis B and C are among the leading causes of death in human immunodeficiency virus (HIV)-infected patients. Prevalence data on viral hepatitis B and C in HIV-infected people in the region of Middle East and North Africa are scarce. We report the prevalence of viral hepatitis B and C in HIV-infected patients in Saudi Arabia. DESIGN AND SETTINGS: Data on all HIV patients who attended HIV Program at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia, were kept longitudinally. For the purpose of this report, patients enrolled in the program between January 1985 and December 2010 were included. METHODS: Data on all HIV patients who received HIV care at age 18 and older between January 1985 and December 2010 were collected. Data were collected from patients' charts at our medical records department and electronically from the electronic health records and HIV database. We excluded patients who were de.ceased prior to completing work-up, lost follow-up, or acquired HIV perinatally. RESULTS: Among 341 HIV-infected patients, hepatitis C infection was found in 41 (12%) patients. The commonest risk factor for hepatitis C virus and HIV acquisition was blood/blood product transfusion in 24 (60%) patients, of these 21 (88%) were hemophiliacs, followed by heterosexual transmission in 9 (22%) patients. The commonest genotype was genotype 1 observed in 18 patients (44%) followed by genotype 4 in 6 (15%) patients. Hepatitis B surface antigen was found in 11 (3%) patients. The commonest risk factor for hepatitis B virus and HIV acquisition was heterosexual transmission in 8 (73%) patients, followed by blood/blood product transfusion in 2 (18%) patients. CONCLUSION: The prevalence of hepatitis C virus and hepatitis B virus infections are, respectively,10 and 20 times higher among HIV-infected patients than in the general population.